The legalisation of cannabis in a growing number of jurisdictions has led to increasing interest in its potential therapeutic effects in a range of disorders, including cutaneous conditions. Cannabinoids have been used as natural medicines for centuries; however, their biological activity in the skin is a new area of study. Recent data suggest that cannabinoids are involved in neuro-immuno-endocrine modulation of skin functioning, yet their effect on the features of dermatologic conditions is unclear. This article sought to review the mechanisms by which cannabinoids regulate skin functioning through the lens of relevance to treatment of dermatologic diseases looking at the effects of cannabinoids on a range of cellular activities and dermatologic conditions both in vitro and in vivo. We identified studies demonstrating an inhibitory effect of cannabinoids on skin inflammation, proliferation, fibrosis, pain, and itch—biological mechanisms involved in the pathogenesis of many dermatologic conditions. Cannabinoids have the potential to expand the therapeutic repertoire of a wide spectrum of skin disorders. Given their widespread unregulated use by the general public, basic and clinical studies are required to elucidate the effectiveness and long-term effects of topical and systemic cannabinoids in cutaneous disorders.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Hughes CE. The trajectories of cannabis and tobacco policies in the United States, Uruguay, Canada and Portugal: is more cross-substance learning possible outside the United States? Addiction. 2018;113(4):603–5.
Biro T, et al. The endocannabinoid system of the skin in health and disease: novel perspectives and therapeutic opportunities. Trends Pharmacol Sci. 2009;30(8):411–20.
Kupczyk P, Reich A, Szepietowski JC. Cannabinoid system in the skin - a possible target for future therapies in dermatology. Exp Dermatol. 2009;18(8):669–79.
Toth KF, et al. cannabinoid signaling in the skin: therapeutic potential of the “C(ut)annabinoid” system. Molecules. 2019;24(5):1223–91.
Solymosi K, Kofalvi A. Cannabis: a Treasure Trove or Pandora’s Box? Mini Rev Med Chem. 2017;17(13):1223–91.
Maccarrone M, et al. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci. 2015;36(5):277–96.
Di Marzo V. New approaches and challenges to targeting the endocannabinoid system. Nat Rev Drug Discov. 2018;17(9):623–39.
Garcia-Gonzalez E, Galeazzi M, Selvi E. Can cannabinoids modulate fibrotic progression in systemic sclerosis? Isr Med Assoc J. 2016;18(3–4):156–8.
Karsak M, et al. Attenuation of allergic contact dermatitis through the endocannabinoid system. Science. 2007;316(5830):1494–7.
Liberati A, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. J Clin Epidemiol. 2009;62(10):e1–34.
Beiteke U, et al. Pain and pain management in dermatology. J Dtsch Dermatol Ges. 2015;13(10):967–87.
Soneji ND, et al. Effects of cannabinoids on capsaicin receptor activity following exposure of primary sensory neurons to inflammatory mediators. Life Sci. 2010;87(5–6):162–8.
Ellington HC, et al. The effect of cannabinoids on capsaicin-evoked calcitonin gene-related peptide (CGRP) release from the isolated paw skin of diabetic and non-diabetic rats. Neuropharmacology. 2002;42(7):966–75.
Maida V, Corban J. Topical medical cannabis: a new treatment for wound pain-three cases of pyoderma gangrenosum. J Pain Symptom Manag. 2017;54(5):732–6.
Malek N, et al. The importance of TRPV1-sensitisation factors for the development of neuropathic pain. Mol Cell Neurosci. 2015;65:1–10.
Oshita K, et al. CB(1) cannabinoid receptor stimulation modulates transient receptor potential vanilloid receptor 1 activities in calcium influx and substance P Release in cultured rat dorsal root ganglion cells. J Pharmacol Sci. 2005;97(3):377–85.
Potenzieri C, et al. Cannabinoid modulation of cutaneous Adelta nociceptors during inflammation. J Neurophysiol. 2008;100(5):2794–806.
Toth CC, et al. Cannabinoid-mediated modulation of neuropathic pain and microglial accumulation in a model of murine type I diabetic peripheral neuropathic pain. Mol Pain. 2010;6:16.
Costa B, et al. The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain. Eur J Pharmacol. 2007;556(1–3):75–83.
Costa B, et al. Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation. Br J Pharmacol. 2004;143(2):247–50.
Nurmikko TJ, et al. Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain. 2007;133(1–3):210–20.
Chelliah MP, et al. Self-initiated use of topical cannabidiol oil for epidermolysis bullosa. Pediatr Dermatol. 2018;35(4):e224–7.
Garibyan L, Rheingold CG, Lerner EA. Understanding the pathophysiology of itch. Dermatol Ther. 2013;26(2):84–91.
Greaves MW. Pathogenesis and treatment of pruritus. Curr Allergy Asthma Rep. 2010;10(4):236–42.
Schlosburg JE, et al. Endocannabinoid modulation of scratching response in an acute allergenic model: a new prospective neural therapeutic target for pruritus. J Pharmacol Exp Ther. 2009;329(1):314–23.
Darmani NA, Pandya DK. Involvement of other neurotransmitters in behaviors induced by the cannabinoid CB1 receptor antagonist SR 141716A in naive mice. J Neural Transm (Vienna). 2000;107(8–9):931–45.
Schlosburg JE, et al. CB1 receptors mediate rimonabant-induced pruritic responses in mice: investigation of locus of action. Psychopharmacology. 2011;216(3):323–31.
Gaffal E, et al. Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors. Allergy. 2013;68(8):994–1000.
Singh D, et al. Dangerous plants in dermatology: legal and controlled. Clin Dermatol. 2018;36(3):399–419.
Petrosino S, et al. Protective role of palmitoylethanolamide in contact allergic dermatitis. Allergy. 2010;65(6):698–711.
Dvorak M, et al. Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflamm Res. 2003;52(6):238–45.
Stander S, Reinhardt HW, Luger TA. Topical cannabinoid agonists An effective new possibility for treating chronic pruritus. Hautarzt. 2006;57(9):801–7.
Eberlein B, et al. Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008;22(1):73–82.
Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat. 2005;13(2):97–103.
Chiurchiu V. Endocannabinoids and immunity. Cannabis Cannabinoid Res. 2016;1(1):59–66.
Chiurchiu V, Battistini L, Maccarrone M. Endocannabinoid signalling in innate and adaptive immunity. Immunology. 2015;144(3):352–64.
Olah A, Szekanecz Z, Biro T. Targeting cannabinoid signaling in the immune system: “High”-ly exciting questions, possibilities, and challenges. Front Immunol. 2017;8:1487.
Namazi MR. Cannabinoids, loratadine and allopurinol as novel additions to the antipsoriatic ammunition. J Eur Acad Dermatol Venereol. 2005;19(3):319–22.
Berdyshev EV. Cannabinoid receptors and the regulation of immune response. Chem Phys Lipids. 2000;108(1–2):169–90.
Norooznezhad AH, Norooznezhad F. Cannabinoids: possible agents for treatment of psoriasis via suppression of angiogenesis and inflammation. Med Hypotheses. 2017;99:15–8.
Ihenetu K, et al. Pharmacological characterisation of cannabinoid receptors inhibiting interleukin 2 release from human peripheral blood mononuclear cells. Eur J Pharmacol. 2003;464(2–3):207–15.
Olah A, et al. Cannabidiol exerts sebostatic and antiinflammatory effects on human sebocytes. J Clin Invest. 2014;124(9):3713–24.
Fischer-Stenger K, Dove Pettit DA, Cabral GA, et al. Delta 9-tetrahydrocannabinol inhibition of tumor necrosis factor-alpha: suppression of post-translational events. J Pharmacol Exp Ther. 1993;267(3):1558–65.
Olah A, et al. Differential effectiveness of selected non-psychotropic phytocannabinoids on human sebocyte functions implicates their introduction in dry/seborrhoeic skin and acne treatment. Exp Dermatol. 2016;25(9):701–7.
Robinson ES, et al. cannabinoid reduces inflammatory cytokines, tumor necrosis factor-alpha, and type i interferons in dermatomyositis in vitro. J Invest Dermatol. 2017;137(11):2445–7.
Wollenberg A, Seba A, Antal AS. Immunological and molecular targets of atopic dermatitis treatment. Br J Dermatol. 2014;170(Suppl 1):7–11.
Mimura T, et al. Involvement of the endogenous cannabinoid 2 ligand 2-arachidonyl glycerol in allergic inflammation. Int Arch Allergy Immunol. 2012;159(2):149–56.
Rockwell CE, et al. A COX-2 metabolite of the endogenous cannabinoid, 2-arachidonyl glycerol, mediates suppression of IL-2 secretion in activated Jurkat T cells. Biochem Pharmacol. 2008;76(3):353–61.
Rockwell CE, et al. Interleukin-2 suppression by 2-arachidonyl glycerol is mediated through peroxisome proliferator-activated receptor gamma independently of cannabinoid receptors 1 and 2. Mol Pharmacol. 2006;70(1):101–11.
Casares L, et al. Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1. Redox Biol. 2019;28:101321.
Stebulis JA, et al. Ajulemic acid, a synthetic cannabinoid acid, induces an antiinflammatory profile of eicosanoids in human synovial cells. Life Sci. 2008;83(19–20):666–70.
Klein TW, et al. Marijuana components suppress induction and cytolytic function of murine cytotoxic T cells in vitro and in vivo. J Toxicol Environ Health. 1991;32(4):465–77.
Glodde N, et al. Differential role of cannabinoids in the pathogenesis of skin cancer. Life Sci. 2015;138:35–40.
Oka S, et al. Suppression by WIN55212-2, a cannabinoid receptor agonist, of inflammatory reactions in mouse ear: interference with the actions of an endogenous ligand, 2-arachidonoylglycerol. Eur J Pharmacol. 2006;538(1–3):154–62.
Fride E, et al. Peripheral, but not central effects of cannabidiol derivatives: mediation by CB(1) and unidentified receptors. Neuropharmacology. 2005;48(8):1117–29.
Lodzki M, et al. Cannabidiol-transdermal delivery and anti-inflammatory effect in a murine model. J Control Release. 2003;93(3):377–87.
Sido JM, Nagarkatti PS, Nagarkatti M. Delta(9)-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells. J Leukoc Biol. 2015;98(3):435–47.
Tubaro A, et al. Comparative topical anti-inflammatory activity of cannabinoids and cannabivarins. Fitoterapia. 2010;81(7):816–9.
Milando R, Friedman A. Cannabinoids: potential role in inflammatory and neoplastic skin diseases. Am J Clin Dermatol. 2019;20(2):167–80.
Pucci M, et al. Epigenetic control of skin differentiation genes by phytocannabinoids. Br J Pharmacol. 2013;170(3):581–91.
Wilkinson JD, Williamson EM. Cannabinoids inhibit human keratinocyte proliferation through a non-CB1/CB2 mechanism and have a potential therapeutic value in the treatment of psoriasis. J Dermatol Sci. 2007;45(2):87–92.
Toth BI, et al. Endocannabinoids modulate human epidermal keratinocyte proliferation and survival via the sequential engagement of cannabinoid receptor-1 and transient receptor potential vanilloid-1. J Invest Dermatol. 2011;131(5):1095–104.
Telek A, et al. Inhibition of human hair follicle growth by endo- and exocannabinoids. FASEB J. 2007;21(13):3534–41.
Dobrosi N, et al. Endocannabinoids enhance lipid synthesis and apoptosis of human sebocytes via cannabinoid receptor-2-mediated signaling. FASEB J. 2008;22(10):3685–95.
Galve-Roperh I, et al. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nat Med. 2000;6(3):313–9.
Grimaldi C, et al. Anandamide inhibits adhesion and migration of breast cancer cells. Exp Cell Res. 2006;312(4):363–73.
Blazquez C, et al. Cannabinoid receptors as novel targets for the treatment of melanoma. FASEB J. 2006;20(14):2633–5.
Casanova ML, et al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. J Clin Invest. 2003;111(1):43–50.
Alexander A, Smith PF, Rosengren RJ. Cannabinoids in the treatment of cancer. Cancer Lett. 2009;285(1):6–12.
Sarfaraz S, et al. Cannabinoids for cancer treatment: progress and promise. Cancer Res. 2008;68(2):339–42.
Armstrong JL, et al. Exploiting cannabinoid-induced cytotoxic autophagy to drive melanoma cell death. J Invest Dermatol. 2015;135(6):1629–37.
Zheng D, et al. The cannabinoid receptors are required for ultraviolet-induced inflammation and skin cancer development. Cancer Res. 2008;68(10):3992–8.
Carpi S, et al. Tumor-promoting effects of cannabinoid receptor type 1 in human melanoma cells. Toxicol In Vitro. 2017;40:272–9.
Gaspari A, Tyring SK. Tyring, clinical and basic immunodermatology, vol. xviii. Dordrecht: Springer; 2009. p. 812.
Wynn TA. Cellular and molecular mechanisms of fibrosis. J Pathol. 2008;214(2):199–210.
Garcia-Gonzalez E, et al. Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts. Rheumatology (Oxford). 2009;48(9):1050–6.
Lazzerini PE, et al. Adenosine A2A receptor activation stimulates collagen production in sclerodermic dermal fibroblasts either directly and through a cross-talk with the cannabinoid system. J Mol Med (Berl). 2012;90(3):331–42.
del Rio C, et al. The cannabinoid quinol VCE-004.8 alleviates bleomycin-induced scleroderma and exerts potent antifibrotic effects through peroxisome proliferator-activated receptor-gamma and CB2 pathways. Sci Rep. 2016;6:21703.
Akhmetshina A, et al. The cannabinoid receptor CB2 exerts antifibrotic effects in experimental dermal fibrosis. Arthritis Rheum. 2009;60(4):1129–36.
Servettaz A, et al. Targeting the cannabinoid pathway limits the development of fibrosis and autoimmunity in a mouse model of systemic sclerosis. Am J Pathol. 2010;177(1):187–96.
Gonzalez EG, et al. Synthetic cannabinoid ajulemic acid exerts potent antifibrotic effects in experimental models of systemic sclerosis. Ann Rheum Dis. 2012;71(9):1545–51.
Goswami R, et al. TRPV4 ION channel is associated with scleroderma. J Invest Dermatol. 2017;137(4):962–5.
Marquart S, et al. Inactivation of the cannabinoid receptor CB1 prevents leukocyte infiltration and experimental fibrosis. Arthritis Rheum. 2010;62(11):3467–76.
Sheriff T, et al. The potential role of cannabinoids in dermatology. J Dermatolog Treat. 2019; p. 1–7.
Mounessa JS, et al. The role of cannabinoids in dermatology. J Am Acad Dermatol. 2017;77(1):188–90.
Marks DH, Friedman A. The therapeutic potential of cannabinoids in dermatology. Skin Ther Lett. 2018;23(6):1–5.
A Phase Ib/IIa, Double-Blind, Randomized Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of S-777469 in Subjects With Atopic Dermatitis. ClinicalTrials.gov Identifier: NCT00697710. https://clinicaltrials.gov/ct2/show/NCT00697710. Accessed 31 Jan 2020.
Trial to Evaluate Efficacy and Safety of Lenabasum in Dermatomyositis. ClinicalTrials.gov Identifier: NCT03813160. https://clinicaltrials.gov/ct2/show/NCT03813160. Accessed 31 Jan 2020.
Trial to Evaluate Efficacy and Safety of Lenabasum in Diffuse Cutaneous Systemic Sclerosis. ClinicalTrials.gov Identifier: NCT03398837. https://clinicaltrials.gov/ct2/show/NCT03398837. Accessed 31 Jan 2020.
Study to Investigate the Efficacy and Safety of Cannabis Oil for the Treatment of Subjects With Hidradenitis Suppurativa. ClinicalTrials.gov Identifier: NCT03929835. https://clinicaltrials.gov/ct2/show/NCT03929835. Accessed 31 Jan 2020.
Topical Acetaminophen for Itch Relief: a Proof of Concept Study in Healthy Subjects. ClinicalTrials.gov Identifier: NCT03997851. https://clinicaltrials.gov/ct2/show/NCT03997851. Accessed 31 Jan 2020.
Conflict of interest
All authors have no conflict of interest to declare.
No funding was received to prepare this review.
Electronic supplementary material
Below is the link to the electronic supplementary material.
About this article
Cite this article
Cintosun, A., Lara-Corrales, I. & Pope, E. Mechanisms of Cannabinoids and Potential Applicability to Skin Diseases. Clin Drug Investig (2020). https://doi.org/10.1007/s40261-020-00894-7